Microarrays have become indispensable tools in research and medicine. DNA microarrays are established as research tools, and they are expected to grow into clinical diagnostics. Higher sensitivity would advance this transition, while also benefiting research. Proteins report more directly on the biology than does DNA or mRNA, protein microarrays have now become commercially available. Protein microarrays present new challenges in design of the substrate because the protein has to remain functional after it is attached to the surface. In addition, higher sensitivity is urgently needed because proteins cannot be amplified by PCR. The proposed product is an innovative microscope slide bearing a thin layer of optically transmissive silica colloidal crystal to impart higher sensitivity by more than 10 fold. This feature alone makes the slide advantageous over any existing slide today. In addition, the silane chemistry allows design of the surface for attachment of DNA, proteins, peptides, lectins, or aptamers as capture agents, and this versatility is unique among high surface-area slides. The proposal focuses on protein microarrays, for which the need is most urgent. The goal is to translate this higher surface area into a sensitivity increase of greater than 10 fold. There are three specific aims. The first will test a model of how sensitivity varies with particle size and biomolecule size. The second will test silane coatings for covalent attachment with minimal loss of function. The third will minimize spot size and wicking by identifying the optimal silane composition. The Phase I research proposed here will establish the feasibility of Phase II research, which will compare bioVidria's slides with commercial slides for two important applications: biomarker discovery and clinical diagnostics. PUBLIC HEALTH RELEVANCE: Nanotechnology is proposed to be used to advance medical research and medical diagnostics. The proposed technology will allow for more sensitive studies of biomarkers and tumors.